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A Self-Reinforced "Microglia Energy Modulator" for Synergistic Amyloid-β Clearance in Alzheimer's Disease Model
Mengmeng Ma, Jing Wang, Kaiming Guo, Wenbin Zhong, Yu Cheng, Li Lin, Yanli Zhao. Angewandte Chemie (International ed. in English), 2025-01-07
Topic: Disease mechanisms in lab and animal studies
Microglial phagocytosis is a highly energy-consuming process that plays critical roles in clearing neurotoxic amyloid-β (Aβ) in Alzheimer's disease (AD). However, microglial metabolism is defective overall in AD, thereby undermining microglial phagocytic functions. Herein, we repurpose the existing antineoplastic drug lonidamine (LND) conjugated with hollow mesoporous Prussian blue (HMPB) as a "microglial energy modulator" (termed LND@HMPB-T7) for safe and synergistic Aβ clearance. The modified blood-brain barrier penetrating heptapeptide (T7) enables efficient transport of LND@HMPB-T7 to the AD brain. LND in LND@HMPB-T7 could fuel Aβ phagocytosis by stimulating microglial adenosine triphosphate (ATP) production, whereas HMPB with catalase and superoxide dismutase-mimicking activities substantially alleviates the mitochondrial side effects commonly associated with LND and thus further enhances ATP production. The synergism of LND and nanozyme affords a high microglial Aβ clearance efficacy without triggering mitochondrial dysfunction. In vivo experiments ascertain that LND@HMPB-T7 could synergistically promote phagocytic clearance of Aβ, relieve neuroinflammation and ameliorate cognitive function in AD mice. These findings indicate that LND@HMPB-T7 holds tremendous clinical potential as a repurposed drug for AD treatment.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ma, M., Wang, J., Guo, K., Zhong, W., Cheng, Y., Lin, L., et al. (2025). A Self-Reinforced "Microglia Energy Modulator" for Synergistic Amyloid-β Clearance in Alzheimer's Disease Model. Angewandte Chemie (International ed. in English). https://doi.org/10.1002/anie.202420547
Vancouver
Ma M, Wang J, Guo K, Zhong W, Cheng Y, Lin L, et al. A Self-Reinforced "Microglia Energy Modulator" for Synergistic Amyloid-β Clearance in Alzheimer's Disease Model. Angewandte Chemie (International ed. in English). 2025. doi:10.1002/anie.202420547. PMID: 39714451.
BibTeX
@article{ma2025-39714451,
author = {Ma, Mengmeng and Wang, Jing and Guo, Kaiming and Zhong, Wenbin and Cheng, Yu and Lin, Li and Zhao, Yanli},
title = {{A Self-Reinforced "Microglia Energy Modulator" for Synergistic Amyloid-β Clearance in Alzheimer's Disease Model}},
journal = {Angewandte Chemie (International ed. in English)},
year = {2025},
doi = {10.1002/anie.202420547},
pmid = {39714451},
url = {https://doi.org/10.1002/anie.202420547}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- However, microglial metabolism is defective overall in AD, thereby undermining microglial phagocytic functions.
- LND in LND@HMPB-T7 could fuel Aβ phagocytosis by stimulating microglial adenosine triphosphate (ATP) production, whereas HMPB with catalase and superoxide dismutase-mimicking activities substantially alleviates the mitochondrial side effects commonly associated with LND and thus further enhances ATP production.
- These findings indicate that LND@HMPB-T7 holds tremendous clinical potential as a repurposed drug for AD treatment.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Angewandte Chemie (International ed. in English)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39714451) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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